Oncolytic viruses as novel anticancer agents: turning one scourge against another

Although the use of viruses as oncolytic agents is an historic concept, the use of genetically modified viruses to selectively target tumour cells is relatively novel and recent. The ability of viruses to efficiently infect a nd lyse cells, combined with the potential augmentation of this effect by p rogeny viruses throughout the tumour provide justification for exploitation of these agents in cancer therapy. Before application to humans, though, i ssues related to tumour cell selectivity, lack of toxicity to normal tissue s and the effect of the antiviral immune response, will have to be clarifie d. The more commonly used oncolytic viruses are based on mutant strains of herpes simplex virus, adenovirus and reovirus. The tumour selectivity of ea ch of these strains is discussed, particularly the complementation of the v iral defect by cellular pathways involved in tumourigenesis. The combinatio n of oncolytic viruses with radiation, chemotherapy and gene therapy is als o reviewed. Further study of the interaction of viral proteins with cellula r pathways involved in cell cycle control will provide the rationale for vi ral mutants with increased selectivity for tumour cells.